| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HCC, non-microsatellite instability-high (MSI-H)/ deficient mismatch repair (dMMR) CRC, PDAC, and BTC |
| CHC, CCR sin inestabilidad de microsatélites alta (MSI-H)/reparación deficiente de emparejamientos erróneos (dMMR), ACDP y CVB. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Liver cancer; Colon cancer; Pancreatic cancer; or Biliary Tract cancer |
| Cáncer de hígado; Cáncer de colon; Cáncer de páncreas; o cáncer de vías biliares |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065252 |
| E.1.2 | Term | Solid tumor |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. To assess the safety and tolerability of the combination of pembrolizumab and lenvatinib and belzutifan.
2. To evaluate the confirmed objective response rate (ORR) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR). |
1.Evaluar la seguridad y la tolerabilidad de la combinación de pembrolizumab, lenvatinib y belzutifán.
2.Determinar la tasa de respuestas objetivas (TRO) confirmadas conforme a los criterios RECIST 1.1, según una evaluación central independiente y con enmascaramiento (ECIE). |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the duration of response (DOR) per RECIST 1.1 as assessed by BICR.
2. To evaluate disease control rate (DCR) per RECIST 1.1 by BICR.
3. To evaluate the progression-free survival (PFS) per RECIST 1.1 as assessed by BICR.
4. To evaluate the overall survival (OS).
5. To evaluate efficacy outcomes per hepatocellular carcinoma (HCC)-specific modified Response Criteria in Solid Tumors version 1.1 (mRECIST 1.1) (Cohort A) assessed by BICR. |
1.Determinar la duración de la respuesta (DR) conforme a los criterios RECIST 1.1, según una ECIE.
2.Determinar la tasa de control de la enfermedad (TCE) conforme a los criterios RECIST 1.1, según una ECIE.
3.Determinar la Supervivencia libre de progresión (SLP) conforme a los criterios RECIST 1.1, según una ECIE
4.Determinar la supervivencia global (SG).
5.Determinar los criterios de valoración de la eficacia conforme a los criterios mRECIST 1.1 específicos del carcinoma hepatocelular (CHC) (cohorte A), según una ECIE. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has histopathologically or cytopathologically documented, advanced solid tumor as follows:
Cohort A HCC
Cohort B CRC (non-MSI-H/dMMR)
Cohort C PDAC
Cohort D BTC (includes intrahepatic, extrahepatic CCA and gall bladder cancer)
2. Participant must have progressed on or since the most recent treatment
3. Has measurable disease per RECIST v1.1 as assessed locally and verified by BICR
4. Submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
5. Participants must fulfill cohort-specific requirements including prior line of therapies
6. Is male or female, at least 18 years of age, at the time of signing the informed consent
7. Male participant is eligible to participate if he agrees to the following during the intervention period with belzutifan or lenvatinib and for at least 7 days after last dose of study intervention with belzutifan or lenvatinib:
•Be abstinent from heterosexual intercourse
OR
• Must agree to use contraception unless confirmed to be azoospermic
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective
9. The participant (or legally acceptable representative if applicable) has provided documented informed consent for the study
10. Has ECOG performance status of 0 to 1 within 7 days of before the start of study intervention
11. Has adequate organ function
12. Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week before start of study treatments.
Cohort A
13. Has a diagnosis of HCC confirmed by histology, or cytology
14. Have BCLC Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
15. Have a Child-Pugh class A liver score within 7 days before first dose of study intervention
16. Participants with past or ongoing HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month before starting study intervention
17. Participants with controlled HBV will be eligible as long as they meet the following criteria:
•Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL before first dose of study intervention. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment
•Participants who are positive for anti-HBc, negative for HbsAg, and negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis
18. Has not received any systemic chemotherapy, including anti-VEGF therapy, anti-PD- 1/PD-L1 or any systemic investigational anticancer agents for advanced/unresectable HCC (1L)
Cohort B
19. Has histopathological documentation of colorectal adenocarcinoma which is advanced (unresectable and metastatic) and not MSI-H or dMMR as documented by a local test report
20. Has received at least 2 prior lines of systemic therapy for unresectable or metastatic disease which includes fluoropyrimidine, irinotecan and oxaliplatin
•Participants with known actionable molecular alterations or biomarker for which an approved therapy exists locally and is available, must have received at least 1 such therapy (eg, BRAF inhibitor-based therapy) for BRAF V600E mutated CRC
Cohort C
21. Has histologically or cytologically confirmed advanced pancreatic ductal adenocarcinoma that is metastatic
Cohort D
22. Have documentation of histopathological diagnosis of CCA (intrahepatic or extrahepatic) or gall bladder cancer (collectively called BTC) and have locally advanced (unresectable) or metastatic disease
23. Participants with past or ongoing HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month before starting study intervention
24. Participants with controlled HBV will be eligible as long as they meet the following criteria:
•Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL before first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment.
•Participants who are positive for anti-HBc, negative for HbsAg, and negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis
25. Received at least 1 prior line of systemic therapy for unresectable or metastatic disease
26. Has a Child-Pugh class A liver score within 7 days before first dose of study intervention |
1Presencia de un tumor sólido avanzad documentado histopatológica o citopatológicamente como sigue:
Cohorte A CHC
Cohorte B CCR (sin MSI-H/dMMR)
Cohorte C ACDP
Cohorte D CVB (incluye colangiocarcinoma intra y extrahepático y cáncer de vesícula biliar)
2Progresión durante o después del tratamiento más reciente.
3Presencia de enfermedad mensurable conforme a RECIST1.1
4Envío de una muestra de tejido tumoral de archivo o de una biopsia reciente, lesión tumoral no irradiada previamente
5Cumplimiento de los requisitos específicos de cada cohorte,incluidas las líneas previas de tratamiento
6Varón o mujer de 18años o más en el momento de firmar el consentimiento informado
7En el estudio podrán participar varones que se comprometan a todo lo siguiente durante el período de intervención con belzutifán o lenvatinib y durante al menos 7días después de recibir la última dosis de la intervención del estudio con belzutifán o lenvatinib:Abstenerse de mantener relaciones heterosexuales O Comprometerse a utilizar métodos anticonceptivos, a menos que se confirme la presencia de azoospermia
8En el estudio podrán participar mujeres que no estén embarazadas ni en período de lactancia y que cumplan al menos una de lo siguiente:No es una mujer en edad fértil O Es una MEF y utiliza un método anticonceptivo eficaz
9El participante ha otorgado su consentimiento informado documentado para el estudio.
10Estado funcional del ECOG de 0-1 en los 7días previos al comienzo de la intervención del estudio
11Presencia de una función orgánica adecuada
12Presión arterial debidamente controlada definida como ≤150/90mmHg sin modificaciones de la medicación antihipertensiva en la semana previa al comienzo de los tratamientos del estudio
Cohorte A
13Diagnóstico de CHC confirmado mediante histología o citología
14Presencia de un tumor en estadio C del BCLC o de un tumor en estadio B del BCLC no susceptible de tratamiento locorregional o resistente a dicho tratamiento y no susceptible de tratamiento curativo
15Puntuación hepática de clase A de Child-Pugh en los 7días previos a la primera dosis de la intervención del estudio
16Podrán participar en el estudio pacientes con infección por el VHC antigua o activa.Los participantes tratados deberán haber completado su tratamiento al menos un mes antes de iniciar la intervención del estudio
17Podrán participar pacientes con infección controlada por el VHB siempre que cumplan los criterios siguientes:Tratamiento antiviral contra el VHB administrado durante al menos 4semanas y carga viral del VHB menor a 500UI/ml.Los participantes en tratamiento activo contra el VHB que presenten una carga viral menor a 100UI/ml deberán mantener el mismo tratamiento durante todo el período de tratamiento del estudio.Los participantes que den positivo para anti-HBc, - para HBsAg y - o + para anti-HBs y que tengan una carga viral del VHB menor a 100UI/ml no precisarán profilaxis antiviral contra el VHB
18No haber recibido quimioterapia sistémica, incluido tratamiento anti-VEGF,anti-PD-1/PD-L1 o cualquier antineoplásico sistémico experimental
Cohorte B
19Documentación histopatológica de adenocarcinoma colorrectal avanzado y sin MSI-H ni dMMR
20.Recepción de al menos dos líneas previas de tratamiento sistémico por enfermedad irresecable o metastásica.Los participantes con alteraciones moleculares susceptibles de actuación conocidas o biomarcadores para los que exista un tratamiento aprobado a nivel local que se encuentre disponible deberán haber recibido al menos un tratamiento de este tipo contra el CCR con mutación BRAF V600E
Cohorte C
21Presencia de un adenocarcinoma ductal de páncreas avanzado y metastásico confirmado histológica o citológicamente
Cohorte D
22Documentación del diagnóstico histopatológico de o cáncer de vesícula biliar y presencia de enfermedad localmente avanzada o metastásica.
23Podrán participar en el estudio pacientes con infección por el VHC antigua o activa.Los participantes tratados deberán haber completado su tratamiento al menos un mes antes de iniciar la intervención del estudio
24Podrán participar pacientes con infección controlada por el VHB siempre que cumplan los criterios siguientes:Tratamiento antiviral contra el VHB administrado durante al menos 4semanas y carga viral del VHB menor a 500UI/ml antes de administrar la primera dosis de la intervención del estudio.Los participantes en tratamiento activo contra el VHB que presenten una carga viral menor a 100UI/ml deberán mantener el mismo tratamiento durante todo el período de tratamiento del estudio.Los participantes que den positivo para anti-HBc, - para HBsAg y - o + para anti-HBs y que tengan una carga viral del VHB menor a 100UI/ml no precisarán profilaxis antiviral contra el VHB
25Recepción de al menos una línea previa de tratamiento sistémico por enfermedad irresecable o metastásica
26Puntuación hepática de clase A de Child-Pugh en los 7días previos a la primera dosis de la intervención del estudio. |
|
| E.4 | Principal exclusion criteria |
1. Is unable to swallow orally administered medication or has a significant GI disorder that may affect study intervention absorption
2. Has a history of a second malignancy that is progressing or has required active treatment within 3 years
3. Has any of the following:
• Hypoxia defined as a pulse oximeter reading <92% at rest, or
• Requires intermittent supplemental oxygen, or
• Requires chronic supplemental oxygen
4. Has known CNS metastases and/or carcinomatous meningitis
5. Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, undergone CABG or PTCA, or cardiac arrhythmia
6. Prolongation of QTc interval to >480 ms
7. Has a LVEF below the institutional (or local laboratory) normal range as determined by MUGA or ECHO
8. Has urine protein ≥1 g/24 hours
9. Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain). A participant who is clinically stable after treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
10. Has preexisting ≥ Grade 3 GI or non-GI fistula
11. Has moderate to severe hepatic impairment (Child-Pugh B or C)
12. Has clinically significant hematuria, hematemesis or hemoptysis (>2.5 mL) of red blood, or other history of significant bleeding within 3 months before screening
13. Has other clinically significant disorders such as:
• Serious active nonhealing wound/ulcer/bone fracture
• Requirement for hemodialysis or peritoneal dialysis
14. Received colony-stimulating factors or transfusion within 28 days before study treatment initiation
15. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
16. Has a history of hypersensitivity reaction to any of the investigational agent(s) included in this study
Medical Conditions – Cohort A (HCC) Only
17. Has had esophageal or gastric variceal bleeding within the last 6 months
18. Has history of clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy
19. Has clinically apparent ascites on physical examination that is not controlled with medication
20. Has inferior vena cava, or cardiac involvement of HCC based on imaging, verified by BICR
21. Has bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants requiring therapeutic INR monitoring e.g. warfarin or similar agents. Treatment with low molecular weight heparin is permitted
22. Has medical contraindications that preclude all forms of contrast enhanced imaging (CT or MRI).
Prior/Concomitant Therapy
23. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
24. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to any costimulatory or coinhibitory T-cell receptor either alone or in combination with another agent in any treatment setting
25. Has received prior radiotherapy within 2 weeks of start of study intervention
26. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
27. Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study
28. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention
Diagnostic Assessments
29. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
30. Has an active autoimmune disease that has required systemic treatment in past 2 years
31. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
32. Has an active infection requiring systemic therapy
33. Has a known history of HIV infection
34. Has a known history of Hepatitis B (defined as HbsAg reactive) or known active Hepatitis C virus
35. For Cohorts A (HCC) and D (BTC): Has dual active HBV infection (HbsAg (+) and /or detectable HBV DNA) and HCV infection (anti-HCV Ab (+) and detectable HCV RNA) at study entry
36. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation
37. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
38. Has radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major blood vessel.
39. Has had an allogenic tissue/solid organ transplant
40. Is pregnant or breastfeeding or expecting to conceive or father children during the study |
1Incapacidad de tragar medicación administrada por vía oral o presencia de un trastorno digestivo importante que pueda afectar a la absorción de la intervención del estudio.
2Antecedentes de una segunda neoplasia maligna que está en progresión o que ha precisado tratamiento activo en los últimos 3años
3Presencia de cualquiera de las circunstancias siguientes:Hipoxia definida como una lectura de pulsioxímetro<92%en reposo.Necesidad de oxigenoterapia intermitente u oxigenoterapia crónica
4Presencia de metástasis en SNC y/o de meningitis carcinomatosa
5Presencia de una enfermedad cardiovascular significativa en los 6meses previos a la primera dosis de la intervención del estudio,como insuficiencia cardíaca congestiva en claseIII oIV de la NYHA,angina de pecho inestable,infarto de miocardio,accidente cerebrovascular,práctica de una revascularización coronaria o ACTP o arritmia cardíaca.
6Prolongación del intervalo QTcF por encima de 480ms
7FEVI por debajo del intervalo normal del centro,determinada mediante MUGA o ECG
8Proteinuria ≥1g/24horas
9.Derrame pleural sintomático.Podrán participar candidatos que se encuentren clínicamente estables tras recibir tratamiento por estos procesos
10Fístula gastrointestinal o no gastrointestinal de grado≥3preexistente
11Insuficiencia hepática moderada o grave
12Presencia de hematuria,hematemesis o hemoptisis clínicamente significativas de sangre roja u otros antecedentes de hemorragia en los 3meses previos a la selección
13Otros trastornos clínicamente significativos como:
Herida, úlcera o fractura ósea activa grave que no cicatriza o consolida
Necesidad de hemodiálisis o diálisis peritoneal
14Recepción de factores estimuladores de colonias o transfusión en los 28días previos al comienzo de la intervención del estudio
15Trastorno psiquiátrico o por abuso de sustancias conocido
16Antecedentes de reacción de hipersensibilidad a cualquiera de los fármacos del estudio,Enfermedades y procesos médicos:cohorteA
17Hemorragia por varices esofágicas o gástricas en los 6últimos meses
18Diagnóstico clínico de encefalopatía hepática en los 6últimos meses sin respuesta al tratamiento
19Ascitis clínicamente evidente en la exploración física que no se controla con medicación
20Invasión de la vena cava inferior o cardias por el CHC según los estudios de imagen confirmada mediante una ECIE
21Presencia de trastornos hemorrágicos o trombóticos o uso de inhibidores del factor X o anticoagulantes que requieran vigilancia terapéutica del INR.Se permite el tratamiento con heparinas de bajo peso molecular
22Presencia de contraindicaciones médicas que impidan realizar todas las formas de estudios de imagen con contraste.Tratamiento previo y concomitante
23Recepción de un tratamiento antineoplásico sistémico previo, incluidos fármacos experimentales,en las 4semanas previas a la asignación
24.Recepción de tratamiento previo con un fármaco anti-PD-1,anti-PD-L1 o anti-PD-L2 o con un fármaco dirigido contra cualquier receptor coestimulador o coinhibidor de los linfocitosT en monoterapia o en combinación con otro fármaco
25Recepción de radioterapia en las 2semanas previas al comienzo de la intervención del estudio
26Recepción de una vacuna de microorganismos vivos o atenuados en los 30días previos a la primera dosis del fármaco del estudio
27ecepción activa de inductores potentes o moderados de la enzimaCYP3A4 que no puedan suspenderse durante el estudio
28Participación activa o pasada en un estudio de un fármaco en investigación o uso de un dispositivo en investigación en las 4semanas previas a la administración de la primera dosis de la intervención del estudio
Evaluaciones diagnósticas
29Diagnóstico de inmunodeficiencia o recepción de tratamiento sistémico crónico con esteroides o cualquier otra forma de tratamiento inmunodepresor en los 7días previos a la primera dosis de la medicación del estudio
30Presencia de una enfermedad autoinmunitaria activa que haya precisado tratamiento sistémico en los 2últimos años
31Antecedentes de neumonitis que haya precisado la administración de esteroides o presencia de una neumonitis activa
32Presencia de una infección activa con necesidad de tratamiento sistémico o por el virus de la inmunodeficiencia humana de la hepatitisB o infección activa conocida por el virus de la hepatitisC.Cohortes Ay D:Infección activa doble por el VHB en el momento de incorporación al estudio
36Antecedentes o datos presentes de cualquier proceso, tratamiento o anomalía analítica que podría confundir los resultados del estudio, dificultar la participación para el posible participante
37Presencia de un trastorno psiquiátrico o por abuso de sustancias que podría dificultar la capacidad del participante
38Signos radiológicos de invasión o infiltración de un vaso sanguíneo importante o de cavitación intratumoral
39Recepción de un alotrasplante
40Embarazo,lactancia o intención de concebir o engendrar un hijo durante el estudio. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Number of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
2. Number of Participants Who Experience at Least One Adverse Event (AE)
3. Number of Participants Who Discontinue Study Treatment Due to an AE
4. Objective Response Rate Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) |
1. Número de participantes que sufren al menos un evento de toxicidad limitante de dosis (DLT)
2. Número de participantes que sufren al menos un evento adverso (AE)
3. Número de participantes que discontinúan el tratamiento de estudio por un AE
4. Ratio de respuesta objetiva por RECIST 1.1 evaluado por un comité central ciego (BICR) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to ~21 days
2. Up to ~45 months
3. Up to ~44 months
4. Up to ~45 months |
. Hasta ~21 días
2. Hasta ~45 meses
3. Hasta ~45 meses
4. Hasta ~45 meses |
|
| E.5.2 | Secondary end point(s) |
1. Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
2. Disease Control Rate (DCR) Per RECIST 1.1 as Assessed by BICR
3. Progression-free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
4. Overall Survival (OS)
5. ORR Per Modified Response Criteria in Solid Tumors Version 1.1 (mRECIST 1.1) for Hepatocellular Carcinoma (HCC) as Assessed by BICR
6. DOR Per mRECIST 1.1 for HCC as Assessed by BICR
7. DCR Per mRECIST 1.1 for HCC as Assessed by BICR
8. PFS Per mRECIST 1.1 for HCC as Assessed by BICR |
1.Determinar la duración de la respuesta (DR) conforme a los criterios RECIST 1.1, según una ECIE.
2.Determinar la tasa de control de la enfermedad (TCE) conforme a los criterios RECIST 1.1, según una ECIE.
3.Determinar la supervivencia libre de progresión (SLP) conforme a los criterios RECIST 1.1, según una ECIE
4.Determinar la supervivencia global (SG).
5.Determinar los criterios de valoración de la eficacia conforme a los criterios mRECIST 1.1 específicos del carcinoma hepatocelular (CHC) (cohorte A), según una ECI
6. DR conforme a los criterios mRECIST 1.1, según una ECIE.
7. TCE conforme a los criterios mRECIST 1.1, según una ECIE.
8. SLP conforme a los criterios RECIST 1.1, según una ECIE |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to ~45 months
2. Up to ~45 months
3. Up to ~45 months
4. Up to ~45 months
5. Up to ~45 months
6. Up to ~45 months
7. Up to ~45 months
8. Up to ~45 months |
1. Hasta ~45 meses
2. Hasta ~45 meses
3.Hasta ~45 meses
4. Hasta ~45 meses
5.Hasta ~45 meses
6. Hasta ~45 meses
7. Hasta ~45 meses
8. Hasta ~45 meses |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 29 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Brazil |
| Canada |
| Chile |
| Israel |
| Korea, Republic of |
| New Zealand |
| Peru |
| Turkey |
| United States |
| Belgium |
| France |
| Germany |
| Ireland |
| Italy |
| Netherlands |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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